Local estrogen therapy used in the management of atrophic vaginitis is generally well tolerated, with serious adverse effects being very rare. The most commonly reported side effects are local and mild, including vaginal irritation, itching, or discharge. Because vaginal estrogen is absorbed primarily locally with minimal systemic absorption, systemic side effects are uncommon and minimal compared to systemic hormone replacement therapy (HRT) NICE NG23.
There is some systemic absorption of vaginal estrogen, but the amount is minimal and unlikely to have significant systemic effects. This minimal absorption means that the risk of systemic estrogen-related side effects, such as increased risk of breast cancer recurrence, remains uncertain but is considered low, especially in estrogen receptor-negative breast cancer patients. However, in patients with estrogen receptor-positive breast cancer, the impact of vaginal estrogen on recurrence risk is unknown, and caution is advised, often requiring specialist input Sulaica et al. 2016 NICE NG23.
Other potential side effects may include mild uterine bleeding or spotting, although this is uncommon with low-dose vaginal preparations. The local application may also cause discomfort or transient burning sensation initially. Overall, the benefits of symptom relief in atrophic vaginitis generally outweigh these minor side effects, and treatment should be regularly reviewed NICE NG23.